tbuckley/cabot-search huggingface dataset:
Selected Articles from This Issue
Journal: Clinical Cancer Research (2020)

Metastatic prostate cancer remains an incurable disease.Treatment with cabozantinib, an oral small-molecule inhibitor of c-Met/VEGFR2 signaling, leads to bone scan responses and significant pain relief but not overall survival improvement in patients with metastatic castration-resistant prostate cancer.To explore the hypothesis that cabozantinib could delay the onset of castration resistance, Corn and colleagues combined cabozantinib with androgen deprivation in patients with hormone-naïve metastatic prostate cancer.Responses in bone scan and measurable disease were observed in 81% of and 90% of evaluable patients, respectively.Elevated plasma concentrations of lumican, CXCL5, CD25, and CD30 and high expression of tumoral pFGFR1 were associated with shorter progression-free survival after treatment.These data suggest that therapy combinations involving cabozantinib are worth further study in metastatic prostate cancer.
Editorial Board and Contents
Authors: Marc Halfon, Maria Diaz-Ortiz, Alice Chen-Plotkin, Teresa Lee, David Katz, Yujin Lee, Junho Choe, Ok Park, Yoon Kim, Angus Davison, Lea Duempelmann, Merle Skribbe, Marc Bühler, Peggy Ozias-Akins, Joann Conner, Caeul Lim, Danielle Loughlin, Jessica Miles, Yvonne Philippo, Patrick Scheffmann, Erik Andersen, Kirsten Bomblies, Martha Bulyk, Ling Chen, Andy Clark, Sue Clark, Susan Gasser, David Goldstein, Leonard Guarente, Yoshihide Hayashizaki, Steven Henikoff, Chris Hittinger, Laurence Hurst, Aldons Lusis, Angela Nieto, Chris Ponting, Claudio Scazzocchio, Bob Schmitz, Nicole Soranzo, Trisha Wittkopp, Joanna Wysocka, Alice Campain
Journal: Trends in Genetics (2020)
Selected Articles from This Issue
Journal: Clinical Cancer Research (2020)

Therapeutic alternatives are limited for aggressive and recurrent meningiomas.Hyperactivation of the mTOR pathway and robust SSTR2A receptor expression has been demonstrated in meningiomas.Based on the authors' preclinical studies that assessed the additive antiproliferative effect of the combination of everolimus and octreotide on meningiomas, Graillon and colleagues initiated a clinical trial using the combination of everolimus and octreotide in aggressive meningiomas not amenable to any form of surgery/radiotherapy.The combination therapy was well-tolerated and resulted in a decline in tumor growth rate, suggesting that the combination of everolimus and octreotide could be considered an option for meningiomas.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2020)

Cells representing a BRCAness phenotype are vulnerable to PARP inhibitors and DNA damaging agents.However, most tumors do not demonstrate a BRCAness phenotype.Although recent studies reveal that BRCAness may be induced through inhibition of CDK12, small-molecule CDK12 inhibitors developed thus far have a narrow therapeutic index.Quereda and colleagues characterized SR-4835, a novel, orally bioavailable ATP-competitive dual inhibitor of CDK12/13, which recapitulated the BRCAness phenotype in triple-negative breast cancer (TNBC).SR-4835 was well tolerated in numerous mouse patient-derived xenograft models and delayed tumor growth when administered as a single agent.Importantly, SR-4835 demonstrated synergy when combined with DNAdamaging agents, leading to tumor regression and significantly increased survival.
Selected Articles from This Issue
Journal: Clinical Cancer Research (2020)

Preclinical studies have revealed CXCR4 as a promising target in multiple myeloma (MM).In a Phase Ib/II clinical trial, Ghobrial and colleagues assessed ulocuplumab, a first-in-class anti-CXCR4 antibody, combined with lenalidomide or bortezomib plus dexamethasone in patients with relapsed MM.This treatment regimen had a favorable safety profile.Particularly in combination with lenalidomide-dexamethasone, ulocuplumab treatment resulted in at least a partial response in over half of patients, with an overall clinical benefit rate of 72.4% and a progression-free survival of over 22 months.Further studies on this treatment regimen are warranted.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2020)

A Novel MYC Inhibitor Sensitizes to Immune Checkpoint BlockadeMYC is critical for tumorigenesis, however, to date it remains untargetable.Han and colleagues utilized a pharmacophore-based in silico screening approach to validate in vitro and in vivo small molecules that disrupted MYC/MAX dimerization and DNA binding.Their lead compound, MYCi361, also induced MYC protein degradation through promoting MYC T58 phosphorylation.MYCi361 had activity against MYC-driven tumors in vitro and in vivo, which was significantly enhanced in immunocompetent models.MYCi361 treatment increased immune tumor infiltration and enhanced anti-PD1 agent activity.Finally, an optimized lead compound (MYCi975) displayed improved in vivo efficacy and tolerability.
Evolving Trends and Widening Racial Disparities in Children Listed for Heart Transplantation in the United States
Authors: M. Mujeeb Zubair, Qiudong Chen, Georgina Rowe, George Gill, Jason Thomas, Shrishiv A. Timbalia, Asishana A. Osho, Michael E. Bowdish, Vikram Sood, Kurt R. Schumacher, Joanna Chikwe, Richard W. Kim
Journal: Circulation (2022)
Correction: Mesenchymal-Type Neuroblastoma Cells Escape ALK Inhibitors
Authors: Ellen M. Westerhout, Mohamed Hamdi, Peter Stroeken, Natalia E. Nowakowska, Arjan Lakeman, Jennemiek van Arkel, Nancy E. Hasselt, Boris Blejlevens, Nurdan Akogul, Franciska Haneveld, Alvin Chan, Peter van Sluis, Danny Zwijnenburg, Richard Volckmann, Carel JM van Noesel, Igor Adameyko, Tim van Gronigen, Jan Koster, Linda J. Valentijn, Johan van Nes, Rogier Versteeg
Journal: Cancer Research (2022)

In the original version of this article (1), there was an issue in Fig. 2B. Specifically, some of the Western blot bands showing expression of DBH, DLK1, PRRX1, SNAI2, and β-actin in the 691-MES/691-ADRN and SH-EP2/SH-SY5Y isogenic neuroblastoma cell lines were previously used in Fig. 1B of a publication by the authors (2). The legend for Fig. 2 has been updated in the latest online HTML and PDF versions of the article (1) to include a citation to the authors’ earlier article in Nature Genetics (2).
Racial and Ethnic Differences in All-Cause and Cardiovascular Disease Mortality: The MESA Study
Authors: Wendy S. Post, Karol E. Watson, Spencer Hansen, Aaron R. Folsom, Moyses Szklo, Steven Shea, R. Graham Barr, Gregory Burke, Alain G. Bertoni, Norrina Allen, James S. Pankow, Joao A.C. Lima, Jerome I. Rotter, Joel D. Kaufman, W. Craig Johnson, Richard A. Kronmal, Ana V. Diez-Roux, Robyn L. McClelland
Journal: Circulation (2022)

Despite improvements in population health, marked racial and ethnic disparities in longevity and cardiovascular disease (CVD) mortality persist. This study aimed to describe risks for all-cause and CVD mortality by race and ethnicity, before and after accounting for socioeconomic status (SES) and other factors, in the MESA study (Multi-Ethnic Study of Atherosclerosis).
Community-Based, Cluster-Randomized Pilot Trial of a Cardiovascular Mobile Health Intervention: Preliminary Findings of the FAITH! Trial
Authors: LaPrincess C. Brewer, Sarah Jenkins, Sharonne N. Hayes, Ashok Kumbamu, Clarence Jones, Lora E. Burke, Lisa A. Cooper, Christi A. Patten
Journal: Circulation (2022)

African Americans continue to have suboptimal cardiovascular health (CVH) based on the American Heart Association Life's Simple 7 (LS7), 7 health-promoting behaviors and biological risk factors (eg, physical activity, blood pressure). Innovative, community-level interventions in partnership with trusted institutions such as African American churches are potential means to improve CVH in this population.
Disparities in Cardiovascular Mortality Between Black and White Adults in the United States, 1999 to 2019
Authors: Ashley N. Kyalwazi, Eméfah C. Loccoh, LaPrincess C. Brewer, Elizabeth O. Ofili, Jiaman Xu, Yang Song, Karen E. Joynt Maddox, Robert W. Yeh, Rishi K. Wadhera
Journal: Circulation (2022)

Background: Black adults experience a disproportionately higher burden of cardiovascular risk factors and disease in comparison with White adults in the United States. Less is known about how sex-based disparities in cardiovascular mortality between these groups have changed on a national scale over the past 20 years, particularly across geographic determinants of health and residential racial segregation. Methods: We used CDC WONDER (Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research) to identify Black and White adults age ≥25 years in the United States from 1999 to 2019. We calculated annual age-adjusted cardiovascular mortality rates (per 100 000) for Black and White women and men, as well as absolute rate differences and rate ratios to compare the mortality gap between these groups. We also examined patterns by US census region, rural versus urban residence, and degree of neighborhood segregation. Results: From 1999 to 2019, age-adjusted mortality rates declined overall for both Black and White adults. There was a decline in age-adjusted cardiovascular mortality among Black (602.1 to 351.8 per 100 000 population) and White women (447.0 to 267.5), and the absolute rate difference (ARD) between these groups decreased over time (1999: ARD, 155.1 [95% CI, 149.9–160.3]; 2019: ARD, 84.3 [95% CI, 81.2–87.4]). These patterns were similar for Black (824.1 to 526.3 per 100 000) and White men (637.5 to 396.0; 1999: ARD, 186.6 [95% CI, 178.6–194.6]; 2019: ARD, 130.3 [95% CI, 125.6–135.0]). Despite this progress, cardiovascular mortality in 2019 was higher for Black women (rate ratio, 1.32 [95% CI, 1.30–1.33])— especially in the younger (age &lt;65 years) subgroup (rate ratio, 2.28 [95% CI, 2.23–2.32])—as well as for Black men (rate ratio, 1.33 [95% CI, 1.32–1.34]), compared with their respective White counterparts. There was regional variation in cardiovascular mortality patterns, and the Black-White gap differed across rural and urban areas. Cardiovascular mortality rates among Black women and men were consistently higher in communities with high levels of racial segregation compared with those with low to moderate levels. Conclusions: During the past 2 decades, age-adjusted cardiovascular mortality declined significantly for Black and White adults in the United States, as did the absolute difference in death rates between these groups. Despite this progress, Black women and men continue to experience higher cardiovascular mortality rates than their White counterparts.
Modulation of the Tumor Immune Microenvironment by Bi<sub>2</sub>Te<sub>3</sub>‐Au/Pd‐Based Theranostic Nanocatalysts Enables Efficient Cancer Therapy
Authors: Fengxia Wu, Haoran Chen, Ruiqi Liu, Yongkuan Suo, Qiqing Li, Youlin Zhang, Hongguang Liu, Zhen Cheng, Yulei Chang
Journal: Advanced Healthcare Materials (2022)

Abstract Nanozymes with multienzyme‐mimicking activities have shown great potential in cancer therapy due to their ability to modulate the complex tumor microenvironment (TME). Herein, a second near‐infrared (NIR‐II) photothermal‐nanocatalyst by decorating Bi 2 Te 3 nanosheets with ultrasmall Au/Pd bimetallic nanoparticles (Bi 2 Te 3 ‐Au/Pd) to reverse the immunosuppressive TME is developed. The peroxidase (POD)‐like and catalase (CAT)‐like activities, and glutathione (GSH) consumption capacity of Au/Pd modulates the TME by disrupting the intracellular redox homeostasis and relieving hypoxia in the TME. Notably, the amplified oxidative stress induces the accumulation of lipid hydroperoxides (LPO) for enhanced ferroptosis. Moreover, upon NIR‐II photoirradiation at 1064 nm, the localized heat generated by Bi 2 Te 3 not only directly ablates the cancer cells but also enhances the Au/Pd‐mediated catalysis‐mediated cancer therapy. Furthermore, both in vitro and in vivo studies confirm that the Bi 2 Te 3 ‐Au/Pd nanocatalysts (BAP NCs) can effectively suppress tumor growth by inducing immunogenic cell death (ICD), and suppressing metastasis and recurrence by the synergistic treatment. Overall, this study provides a promising theranostic strategy for effective tumor inhibition.
Acoustic regularities in infant-directed speech and song across cultures
Authors: Courtney B. Hilton, Cody J. Moser, Mila Bertolo, Harry Lee-Rubin, Dorsa Amir, Constance M. Bainbridge, Jan Simson, Dean Knox, Luke Glowacki, Elias Alemu, Andrzej Galbarczyk, Grazyna Jasienska, Cody T. Ross, Mary Beth Neff, Alia Martin, Laura K. Cirelli, Sandra E. Trehub, Jinqi Song, Minju Kim, Adena Schachner, Tom A. Vardy, Quentin D. Atkinson, Amanda Salenius, Jannik Andelin, Jan Antfolk, Purnima Madhivanan, Anand Siddaiah, Caitlyn D. Placek, Gul Deniz Salali, Sarai Keestra, Manvir Singh, Scott A. Collins, John Q. Patton, Camila Scaff, Jonathan Stieglitz, Silvia Ccari Cutipa, Cristina Moya, Rohan R. Sagar, Mariamu Anyawire, Audax Mabulla, Brian M. Wood, Max M. Krasnow, Samuel A. Mehr
Journal: Nature Human Behaviour (2022)
Covid continues to disrupt: what is the plan to deal with it?
Authors: Layla McCay
Journal: BMJ (2022)

Covid continues to disrupt: what is the plan to deal with it?Layla McCay director of policy NHS staff are starting to feel like it's Groundhog Day: healthcare is yet again being derailed by the march of covid-19.While fortunately this time round people are generally not becoming as ill as in previous waves, the current subvariants are proving adept at evading immune defences and spreading rapidly.
Unfolded Protein Response Differentially Modulates the Platelet Phenotype
Authors: Kanika Jain, Tarun Tyagi, Jing Du, Xiaoyue Hu, Kanchi Patell, Kathleen A. Martin, John Hwa
Journal: Circulation Research (2022)

Background: Unfolded protein response (UPR) is a multifaceted signaling cascade that alleviates protein misfolding. Although well studied in nucleated cells, UPR in absence of transcriptional regulation has not been described. Intricately associated with cardiovascular diseases, platelets, despite being anucleate, respond rapidly to stressors in blood. We investigate the UPR in anucleate platelets and explore its role, if any, on platelet physiology and function. Methods: Human and mouse platelets were studied using a combination of ex vivo and in vivo experiments. Platelet lineage-specific knockout mice were generated independently for each of the 3 UPR pathways, PERK (protein kinase RNA [PKR]-like endoplasmic reticulum kinase), XBP1 (X-binding protein), and ATF6 (activating transcription factor 6). Diabetes patients were prospectively recruited, and platelets were evaluated for activation of UPR under chronic pathophysiological disease conditions. Results: Tunicamycin induced the IRE1α (inositol-requiring enzyme-1alpha)-XBP1 pathway in human and mouse platelets, while oxidative stress predominantly activated the PERK pathway. PERK deletion significantly increased platelet aggregation and apoptosis and phosphorylation of PLCγ2, PLCβ3, and p38 MAPK. Deficiency of XBP1 increased platelet aggregation, with higher PLCβ3 and PKCδ activation. ATF6 deletion mediated a relatively modest effect on platelet phenotype with increased PKA (protein kinase A). Platelets from diabetes patients exhibited a positive correlation between disease severity, platelet activation, and protein aggregation, with only IRE1α-XBP1 activation. Moreover, IRE1α inhibition increased platelet aggregation, while clinically approved chemical chaperone, sodium 4-phenylbutyrate reduced the platelet hyperactivation. Conclusions: We show for the first time, that UPR activation occurs in platelets and can be independent of genomic regulation, with selective induction being specific to the source and severity of stress. Each UPR pathway plays a key role and can differentially modulate the platelet activation pathways and phenotype. Targeting the specific arms of UPR may provide a new antiplatelet strategy to mitigate thrombotic risk in diabetes and other cardiovascular diseases.
Polygenic Risk Scores for Cardiovascular Disease: A Scientific Statement From the American Heart Association
Authors: Jack W. O’Sullivan, Sridharan Raghavan, Carla Marquez-Luna, Jasmine A. Luzum, Scott M. Damrauer, Euan A. Ashley, Christopher J. O’Donnell, Cristen J. Willer, Pradeep Natarajan
Journal: Circulation (2022)

Cardiovascular disease is the leading contributor to years lost due to disability or premature death among adults. Current efforts focus on risk prediction and risk factor mitigation' which have been recognized for the past half-century. However, despite advances, risk prediction remains imprecise with persistently high rates of incident cardiovascular disease. Genetic characterization has been proposed as an approach to enable earlier and potentially tailored prevention. Rare mendelian pathogenic variants predisposing to cardiometabolic conditions have long been known to contribute to disease risk in some families. However, twin and familial aggregation studies imply that diverse cardiovascular conditions are heritable in the general population. Significant technological and methodological advances since the Human Genome Project are facilitating population-based comprehensive genetic profiling at decreasing costs. Genome-wide association studies from such endeavors continue to elucidate causal mechanisms for cardiovascular diseases. Systematic cataloging for cardiovascular risk alleles also enabled the development of polygenic risk scores. Genetic profiling is becoming widespread in large-scale research, including in health care-associated biobanks, randomized controlled trials, and direct-to-consumer profiling in tens of millions of people. Thus, individuals and their physicians are increasingly presented with polygenic risk scores for cardiovascular conditions in clinical encounters. In this scientific statement, we review the contemporary science, clinical considerations, and future challenges for polygenic risk scores for cardiovascular diseases. We selected 5 cardiometabolic diseases (coronary artery disease, hypercholesterolemia, type 2 diabetes, atrial fibrillation, and venous thromboembolic disease) and response to drug therapy and offer provisional guidance to health care professionals, researchers, policymakers, and patients.
Editor's Note: Immortalization of Primary Human Prostate Epithelial Cells by c-Myc
Authors: Jesús Gil, Preeti Kerai, Matilde Lleonart, David Bernard, Juan Cruz Cigudosa, Gordon Peters, Amancio Carnero, David Beach
Journal: Cancer Research (2022)

We were informed by the authors that in Fig. 1B, the panels showing E7-and mdm2-expressing cells originated from the same picture of mdm2-expressing
Aging induces severe SIV infection accompanied by an increase in follicular CD8+ T cells with overactive STAT3 signaling
Authors: Hong-Yi Zheng, Xue-Hui Wang, Xiao-Yan He, Min Chen, Ming-Xu Zhang, Xiao-Dong Lian, Jia-Hao Song, Yan Hu, Wei Pang, Yun Wang, Zheng-Fei Hu, Long-Bao Lv, Yong-Tang Zheng
Journal: Cellular and Molecular Immunology (2022)
Single-Cell Sequencing Reveals Trajectory of Tumor-Infiltrating Lymphocyte States in Pancreatic Cancer
Authors: Aislyn Schalck, Donastas Sakellariou-Thompson, Marie-Andrée Forget, Emi Sei, Tara G. Hughes, Alexandre Reuben, Shanshan Bai, Min Hu, Tapsi Kumar, Mark W. Hurd, Matthew H.G. Katz, Ching-Wei D. Tzeng, Shubham Pant, Milind Javle, David R. Fogelman, Anirban Maitra, Cara L. Haymaker, Michael P. Kim, Nicholas E. Navin, Chantale Bernatchez
Journal: Cancer Discovery (2022)

Pancreatic ductal adenocarcinoma (PDAC) has few effective treatments. Immunotherapy, an attractive alternative strategy, remains challenging with the lack of knowledge on the tumor-infiltrating lymphocyte (TIL) landscape in PDAC. To generate a reference of T-cell subpopulations, we profiled 80,000 T cells from 57 PDAC samples, 22 uninvolved/normal samples, and cultured TIL using single-cell transcriptomic and T-cell receptor analysis. These data revealed 20 cell states and heterogeneous distributions of TIL populations. The CD8+ TIL contained a putative transitional GZMK+ population based on T-cell receptor clonotype sharing, and cell-state trajectory analysis showed similarity to a GZMB+PRF1+ cytotoxic and a CXCL13+ dysfunctional population. Statistical analysis suggested that certain TIL states, such as dysfunctional and inhibitory populations, often occurred together. Finally, analysis of cultured TIL revealed that high-frequency clones from effector populations were preferentially expanded. These data provide a framework for understanding the PDAC TIL landscape for future TIL use in immunotherapy for PDAC. To improve the efficacy of immunotherapy in PDAC, there is a great need to understand the PDAC TIL landscape. This study represents a reference of PDAC TIL subpopulations and their relationships and provides a foundation upon which to base future immunotherapeutic efforts. This article is highlighted in the In This Issue feature, p. 2221.
Modeling global 80-80-80 blood pressure targets and cardiovascular outcomes
Authors: Sarah J. Pickersgill, William T. Msemburi, Laura Cobb, Nicole Ide, Andrew E. Moran, Yanfang Su, Xinpeng Xu, David A. Watkins
Journal: Nature Medicine (2022)

Abstract As the leading cause of death worldwide, cardiovascular diseases (CVDs) present major challenges for health systems. In this study, we analyzed the effects of better population blood pressure control in the context of a proposed 80-80-80 target: 80% of individuals with hypertension are screened and aware of their diagnosis; 80% of those who are aware are prescribed treatment; and 80% of those on treatment have achieved guideline-specified blood pressure targets. We developed a population CVD model using country-level evidence on CVD rates, blood pressure levels and hypertension intervention coverage. Under realistic implementation conditions, most countries could achieve 80-80-80 targets by 2040, reducing all-cause mortality by 4–7% (76–130 million deaths averted over 2022–2050) and slowing the rise in CVD expected from population growth and aging (110–200 million cases averted). Although populous middle-income countries would account for most of the reduced CVD cases and deaths, low-income countries would experience the largest reductions in disease rates.
A Process Framework for Ethically Deploying Artificial Intelligence in Oncology
Authors: Andrew Hantel, Dillon D. Clancy, Kenneth L. Kehl, Jonathan M. Marron, Eliezer M. Van Allen, Gregory A. Abel
Journal: Journal of Clinical Oncology (2022)

2][3] The use of AI in cancer care is rapidly expanding: a May 2022 PubMed search of the term cross-referenced with cancer revealed approximately 26,000 citations, with more than 60% published in the past five years.4][5] Relative to other parts of medicine, the implications of oncology AI are outsized, and some are idiosyncratic.Oncology AI tools apply to not one but two genomes (germline and somatic); can greatly complicate the existing weight of bias, discrimination, and structural racism in cancer care; and can subtly undermine patient and physician autonomy, leading to cancer care that is algorithmic rather than patientcentered.These diverse concerns, in the context of unreserved enthusiasm for AI, challenge a future where oncology AI is both widely implemented and ethically acceptable.We propose that adapting a processfocused approach for deploying AI in cancer care, such as the accountability for reasonableness framework (A4R), 6 can address these concerns and realize a future where oncology AI is ethically deployed.